New molecular probes are proposed which combine a fluorescent component and a novel, covalently linked gold particle with very low non-specific protein binding. These probes will be used to study nuclear processes in living cells: the fluorescent markers will allow imaging of dynamic cell processes and 3-D nuclear architecture at a level of sensitivity up to an order of magnitude or more over current levels in the confocal microscope. The gold probe, will provide ultrastructural details of cells frozen at a specific stage or optimal staining level. Elimination of staining procedures between the two observations will enable a new level of accuracy in correlation between results. The new probes should combine improved sensitivities with penetration up to 30 mum into cells and tissue sections. Applications in genetics and DNA sequencing will be pursued.